A phase II study has shown activity of recombinant adenovirus interferon-α with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, in patients with high-grade bacillus Calmette-Guerin (BCG)-refractory or -relapsed non–muscle invasive bladder cancer. These findings were reported by Shore et al in the Journal of Clinical Oncology. Syn3 is a polyamide surfactant incorporated into rAd-IFNα to increase adenoviral transduction of the bladder lining.
In the multicenter study, 40 evaluable patients with BCG-refractory (n = 21) or -relapsed (n = 19) non–muscle invasive bladder cancer were randomized between November 2012 and April 2015 to received intravesical rAd-IFNα/Syn3 at 1 x1011 (n = 21) or 3 x 1011 (n = 19) viral particles/mL. Patients with response at months 3, 6, and 9 were re-treated at months 4, 7, and 10. The primary endpoint was 12-month high-grade disease recurrence-free survival.
At 12 months, 14 patients (35.0%) remained free of high-grade recurrence, with response rates of 33% in the lower-dose group and 37% in the higher-dose group. Among these 14 patients, 2 had recurrence at 21 and 28 months, and 1 died of an upper genitourinary tract tumor at 17 months without recurrence. Overall, median time to high-grade disease recurrence was 3.5 months in the low-dose group and 11.7 months in the high-dose group.
Grade 3 adverse events occurred in 22% of patients. No grade ≥ 4 adverse events were observed, and no patients discontinued treatment due to adverse events. The most common drug-related adverse events were micturition urgency (40%), dysuria (40%), fatigue (32.5%), pollakiuria (28%), hematuria (25%), and nocturia (25%).
The investigators concluded: “rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with [high-grade non–muscle invasive bladder cancer] after BCG therapy who were unable or unwilling to undergo radical cystectomy.”
The study was supported by FKD Therapies Oy and National Cancer Institute grants.
Colin P.N. Dinney, MD, of The University of Texas MD Anderson Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
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